To study the factors which regulate growth and morphology of gallbladder cancer, we have examined those of normal gallbladder cell and cell lines of gallbladder cancer in three-dimensioned collagen gels.Primary normal gallbladder cell formed cystic structure, which was enhanced by addition of EGF,HGF or epimorphin, whereas there were variations in the degree of the effects. On the contrary the subcultued cells had not formed cystic structure, but the addition of conditioned medium of fibroblasts or coculture with fibroblasts made them cystic. It was suggested that fibroblasts secrete some factor(s) which promotes regain of the cystic morphogenesis.On the other hand, gallbladder cancer cell lines rarely show cystic structure in collagen gels, and the above factors did not promote the cystic formation. Only GB-d1 formed cystic structure especially in floating collagen gel. EGF,HGF and conditioned medium of fibroblasts had the tendencies to stimulate the morphogenesis for branching or tubular formation.The above-mentioned differences between the normal and cancer cells supposed to be caused by the differences of intracellular signal transduction or those of the expressions of some adhesion molecules.